This research demonstrates the sequence specific suppression of HIV replication using HIV-1 antibody-targeted liposomes containing antisense phosphorothioate oligonucleotides. Liposomes were generated which encapsulated the 20-mer sequence of the rev HIV-1 regulatory gene in the form of a phosphorothioate oligonucleotide. Specific targeting of the liposome was accomplished by conjugating HIV positive human IgG to the surface of the liposome resulting in the formation of an immunoliposome. HIV-1 infected H9 cells incubated with the immunoliposomes were rendered less permissive for viral replication. As compared with the positive control, HIV replication was reduced by almost 95%. Inhibition of HIV replication was not observed using empty liposomes containing random phosphorothioate oligomer sequences. These immunoliposomes exhibit dual specificity: a targeting antibody on the surface of the liposome specific for infected cells, and, inside the immunoliposomes, an oligomer with antiviral activity that is complementary to a specific portion of the mRNA of the infected cell. The antiviral activity of the free and the encapsulated oligonucleotides was assessed by p24 antigen ELISA, reverse transcriptase assay, Western blot, immunofluorescense, and PCR analysis. Liposome preparations demonstrated minimal toxicity in H9 cell culture experiments. Results using targeted antisense liposomes suggest tha the mechanism for the inhibition of viral expression is its interaction with the rev regulatory gene resulting in translation arrest. These in vitro culture results demonstrate the potential efficacy of drug-encapsulated immunoliposomes in the treatment of AIDS and AIDS related complex.